Administration of 2-butoxyethanol (BE) or 2-methoxyethanol to rats by gavage induced dose-dependent acute hemolytic anemia and testicular toxicity, respectively. Early reports from this laboratory indicated that calcium channel lockers protect against the testicular toxicity of 2-methoxyethanol. The present work investigated the effect of calcium channel blockers against BE-induced hemolytic anemia. Treatment of rats with calcium channel blockers, verapamil (40 mg/kg: ip) or diltiazem (90 mg/kg: ip) prior to BE administration resulted in a significant (decrease in erythrocytic swelling, ATP depletion, and ameliorated the subsequent BE-induced hemolytic anemia. In vitro, addition of verapamil or diltiazem, at concentrations ranging from 0.25 to 2.0 milli-M. to blood prior to incubation with BAA, resulted in a time- and concentration-dependent attenuation of swelling, ATP depletion, and hemolysis of erythrocytes. Incubation of erythrocytes with BAA in calcium-free media or addition of EGTA had no effect on BAA activity.